FDA Restricts Use of High Doses of Cholesterol-Lowering Drug Zocor

The Food and Drug Administration (FDA) on Wednesday restricted the use of high doses of the cholesterol-lowering drug simvastatin, which is sold in generic forms and under the brand names Zocor and Vytorin, because of concerns over muscle problems associated with the drug.

The agency recommends that no new patients start taking the highest dose, 80 mg, of the medication. However, those who are already safely taking that dose may continue to do so.

Statins, which lower cholesterol by inhibiting its production in the liver, are among the most commonly prescribed drugs in the U.S. Recent studies have shown that the medications can lower the risk of having a heart attack or dying from heart disease, but the drugs have also been linked to serious side effects.

The statin Baycol (cerivastatin) was recalled in 2001 after users reported elevated rates of muscle injury similar to the ones that led the FDA to restrict use of simvastatin. Concerns about simvastatin and its potential to cause muscle-weakening, known as myopathy, emerged last March when the FDA issued warnings about the risk.

The changes to the label for simvastatin-containing medications are based on the FDA’s review of the seven-year Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine clinical trial, other clinical trial data, and analyses of adverse events submitted to the FDA’s Adverse Event Reporting System. All showed that patients taking simvastatin 80 mg daily had an increased risk of muscle injury compared to patients taking lower doses of simvastatin or other statin drugs. The risk of muscle injury is highest during the first year of treatment with the 80 mg dose of simvastatin, is often the result of interactions with certain other medicines, and is frequently associated with a genetic predisposition for simvastatin-related muscle injury.

Because the peak of symptoms occurs in the first year of use, FDA officials advise people who have taken simvastatin for more than a year without any muscle issues to continue with their medication. But doctors should not increase dosing from 40 mg to 80 mg in patients to try to get cholesterol levels under control.

Merck, simvastatin’s manufacturer, launched a website with information on the new restrictions, and heart experts strongly recommend that patients on the medication consult with their doctor about how the new ruling affects them. The drug was approved in 1991, and some heart experts believe the agency should have acted sooner to warn patients and doctors about its risk. On heartwire, Dr. Steven Nissen, a cardiologist at the Cleveland Clinic Foundation who has previously raised the alarm about muscle issues related to the medication, said:

Most knowledgeable lipid experts stopped administering the 80 mg dosage of simvastatin years ago. Unfortunately, once again the FDA has been slow to react to a serious drug safety problem. I’m glad the FDA acted but wish they hadn’t taken so long.

What does the decision mean for other statins? Dr. Ralph Sacco, president of the American Heart Association and chairman of neurology at University of Miami, says, “In terms of trying to generalize to other statins, it’s always difficult. All statins are not exactly the same; there are different chemical structures of these drugs so we shouldn’t jump to the conclusion that if [muscle problems] occur in one it has to be true of the others.”

Sacco notes that one reason the FDA restricted new prescriptions of high-dose simvastatin is that there are other statins on the market that provide similar if not better cholesterol-lowering benefits with potentially less risk.